18th International Myeloma Workshop

Iberdomide in combination with dexamethasone and daratumumab, bortezomib, or carfilzomib in RRMM patients

Prof Sagar Lonial - Winship Cancer Institute of Emory University, Atlanta, USA

This study is a phase I expansion trial that is evaluating iberdomide in combination with bortezomib, daratumumab and carfilzomib. We’ve demonstrated that iberdomide as a single agent and in combination with dexamethasone has significant activity in the triple class refractory patient population and, more importantly, in patients that are resistant to pomalidomide. While its mechanism is similar, in that it binds cereblon, it does so more potently and is able to induce different downstream pathways that allows it to be active. The goal of this study was really to evaluate the dose escalation in combinations with bortezomib, daratumumab and carfilzomib.

What was the methodology used in this study?

In terms of methodology this was a phase I expansion dose escalation study where we used increasing doses of bortezomib, a fixed dose of daratumumab with different doses of iberdomide and increasing doses of iberdomide in combination with carfilzomib. Again, the goal was to identify the maximum tolerated dose for each of these three cohorts.

What were your findings?

What I think we were really excited to see was that in each of these three dosing cohorts we were able to escalate to full doses. We now are at full dose of iberdomide with daratumumab, we are at full dose of iberdomide with bortezomib and are two-thirds of the way up the dose escalation with iberdomide plus carfilzomib. So hopefully we will see full doses of both of those in the combination as well. What we have noted is no new adverse events and we have also noted that the response rate, even in the context of resistant disease to either bortezomib, daratumumab or carfilzomib, we’re able to see pretty good response rates for the combination with iberdomide, suggesting we may have synergy between these combinations and even able to overcome drug resistance.

How can these results impact the future treatment of rrMM?

We know that iberdomide clearly is an active agent, even in triple class refractory myeloma. The goals of these studies were to give doses and schemas for subsequent phase III trials. As with every drug we use in myeloma when it works in the refractory setting we start moving it into earlier and earlier settings. There are, in fact, trials planned looking at iberdomide daratumumab dexamethasone, iberdomide bortezomib dexamethasone and potentially even iberdomide carfilzomib dexamethasone versus other standard treatments in phase III trials to demonstrate the activity of this new cell mod with standard myeloma treatments, hopefully leading to new combinations with second and third generation agents.